The long term objectives of this project are to contribute to an understanding of the role of glycolipids in cell physiology and of the pathological processes involved in the clinical manifestations of Fabry's disease. The known dramatic effects of testosterone on the kidney glycolipids (primarily galabiosylceramide) of the mouse will be utilized to investigate regulation of glycolipid metabolism. Quantitative high performance liquid chromatography, radioisotope labelling studies and analysis of synthetic and degradative enzymes will be employed. Structural studies of kidney glycolipids will utilize classical and combined gas chromatography-mass spectrometric procedures. Various mouse strains, animal species and taxa will be examined for the presence of hormonal effects on kidney glycolipids. The toad (Bufo Marinus) bladder which contains a lipid similar to galabiosylceramide as a major component, will be examined as a possible in vitro model system of the mammalian distal tubule and collecting duct for the study of glycolipid function. The morphological distribution of glycolipids will be investigated by microdissection and immunohistochemical methods. Possible hormonal effects on glycolipid metabolism in humans will be investigated for their importance in the clinical expression of Fabry's disease. The urinary excretion of galabiosylceramide, which originates from the kidney, will be measured in prepubescent and pubescent normal and Fabry's disease individuals. The known male-female difference in the level globotriaosylceramide in human plasma will be further analyzed by longitudinal studies of normals and Fabry's disease patients. Possible correlations of the plasma and urine levels of glycosphingolipid and alpha-galactosidase A with clinical expression in Fabry's hemi- and heterozygotes will also be sought.